pH-RESPONSIVE POLYMER CARRIER COMPOSITIONS FOR CYTOSOLIC PROTEIN DELIVERY - pH-Responsive polymer-based protein delivery carriers and compositions, methods for making the carriers and compositions, and methods for using the carriers and compositions for intracellular protein antigen delivery, inducing a cytotoxic T-lymphocyte response, introducing a tumor-specific protein antigen to an antigen presenting cell to induce an immune response, and providing tumor protection to a subject.

06-17-2010

20100160216

ENHANCED TRANSPORT USING MEMBRANE DISRUPTIVE AGENTS - Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes (at physiologic pH, but can become active toward cell membranes if the environment is acidified below ca. pH 6.8), coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontopheresis, and/or electrophereis can also be used with the disrupting agents.

06-24-2010

20100210504

ENHANCED TRANSPORT USING MEMBRANE DISRUPTIVE AGENTS - Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes (at physiologic pH, but can become active toward cell membranes if the environment is acidified below ca. pH 6.8), coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontopheresis, and/or electrophereis can also be used with the disrupting agents.

System and Method for Magnetically Concentrating and Detecting Biomarkers - System and method for capturing, concentrating, and detecting a diagnostic target in a liquid, comprising applying a magnetic field to a mixture comprising a co-aggregate in the liquid to provide a collected co-aggregate in the liquid, wherein the co-aggregate comprises a magnetic particle having a stimuli-responsive polymer attached thereto and a non-magnetic particle having a stimuli-responsive polymer and a diagnostic target attached thereto.

01-06-2011

20110117668

SELF-POWERED SMART DIAGNOSTIC DEVICES - Devices and methods are provided for immobilizing a diagnostic target (e.g., indicative of a disease) from a solution (e.g., a biological fluid). The diagnostic target is first bound to a capture conjugate that includes a reversibly-associative polymer moieties attached to a first binding moiety that binds to the diagnostic target. Once the diagnostic target is bound to the capture conjugate, the solution is subjected to a change in heat and/or pH to cause the reversibly-associative polymer moieties to aggregate. The aggregates are then immobilized (e.g., via filtration).

DIBLOCK COPOLYMERS AND POLYNUCLEOTIDE COMPLEXES THEREOF FOR DELIVERY INTO CELLS - Described herein are copolymers, and methods of making and utilizing such copolymers. Such copolymers have at least two blocks: a first block that has at least one unit that is hydrophilic at physiologic pH, and a second block that has hydrophobic groups. This second block further has at least one unit with a group that is anionic at about physiologic pH. The described copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the copolymer is endosomolytic.

06-16-2011

20110143435

POLYMERIC CARRIER - Provided herein are polymeric carriers suitable for the delivery of polynucleotides (e.g. oligonucleotides) and/or other therapeutic agents into a living cell.

BISPECIFIC INTRACELLULAR DELIVERY VEHICLES - A composition for delivering an agent to a cell, comprising a bispecific affinity reagent and a pH-responsive, membrane destabilizing polymer. The bispecific affinity reagent may include a first affinity reagent covalently linked to a second affinity reagent, wherein the first affinity reagent binds to a molecule on the surface of a cell, and the second affinity reagent binds to an intracellular target.

POLYMER BLEND PARTICLES FOR INTRACELLULAR DELIVERY OF AGENTS - Core-shell polymer blend particles are described. The particles include a pH-responsive polymeric shell and a pH-irresponsive polymeric core. The core can include a biodegradable hydrolysable polymer and the shell can include a pH-responsive copolymer that can include constitutional units that are cationic and/or anionic at physiological pH. The core-shell polymer blend particles can allow the controlled delivery of agents into a plurality of distinct intracellular compartments.